Randomized Phase 3 Study Evaluation the Efficacy and Safety of Oral Azacitidine(CC-486) Compared to Investigator's Choice Therapy in Patients With Relapsed or Refractory Angioimmunoblastic T Cell Lymphoma
Overview
- Phase
- Phase 3
- Intervention
- Azacitidine
- Conditions
- Lymphoma, T-Cell
- Sponsor
- Celgene
- Enrollment
- 93
- Locations
- 12
- Primary Endpoint
- Progression Free Survival (PFS) Based on Local Assessment
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
This study is a multicentric, open-label, randomized phase 3 trial. The study will be conducted in select countries in Europe and South Korea sponsored by LYSARC and in Japan sponsored by Celgene. There will be a combined enrollment target of 86 randomized patients, with approximately 14 randomized patients from Japan.
The enrollment to the randomized study will start at European sites in parallel to a safety run-in part in Japan. A safety run-in will be conducted to confirm the tolerability of oral azacitidine at doses of 100 mg and 200 mg QD in Asian patients. Once oral azacitidine at 200 mg QD is confirmed as tolerable, Asian patients from Japan and South Korea will start to be randomized into the main study. Additional patients (non-randomized) are anticipated to enroll to the safety run-in.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient is ≥ 18 years of age at the time of signing the informed consent form (ICF).
- •Patient must understand and voluntarily sign an ICF prior to any study-specific assessments/procedures being conducted.
- •Patient is willing and able to adhere to the study visit schedule and other protocol requirements
- •Patient had local diagnosed peripheral T cell lymphoma (PTCL) with T-follicular helper (TFH) phenotype according to the criteria of the latest WHO classification based on a surgical lymph node biopsy or needle core biopsy including any one of
- •Angioimmunoblastic T cell lymphoma (AITL)
- •Follicular T cell lymphoma
- •Nodal peripheral T-cell lymphoma with TFH phenotype There should be a documented expression of minimum two TFH markers among this panel of markers: CD10, CXCL13, PD1, ICOS and BCL6 by the tumoral cells by immunohistochemistry. Biopsy at relapse or progression is not mandatory, but highly encouraged on a surgical or needle core biopsy, and diagnostic tissue should be available for central pathology review and for ancillary molecular studies.
- •Local pathology report should be reviewed by the sponsor's medical monitor prior to enrollment.
- •ECOG performance status 0 to 3
- •Relapsed (after partial or complete response) or refractory AITL after at least one line of systemic therapy (there is no mandatory resting period after the previous treatment as long as the biochemistry and hematology labs meet the inclusion criteria as below.)
Exclusion Criteria
- •Clinical evidence of central nervous system(CNS) involvement by lymphoma. Patients with suspicion of CNS involvement must undergo neurologic evaluation and CT/MRI of head and lumbar puncture to exclude CNS disease.
- •Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator's decision)
- •Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
- •Known Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV) infection, or evidence of active Hepatitis B Virus (HBV) infection defined as:
- •HBs Ag positive
- •HBs Ag negative, anti-HBs antibody positive and/or anti-HBc antibody positive with detectable viral DNA
- •Impaired renal function (calculated MDRD or Cockcroft-Gault Creatinine Clearance \< 30 ml/min) or impaired liver function tests (Serum total bilirubin level \> 2.0 mg/dl \[34 μmol/L\] (except in case of Gilbert's Syndrome, or documented liver or pancreatic involvement by lymphoma), Serum transaminases (AST or ALT) \> 3 upper normal limits) unless they are related to the lymphoma.
- •Active malignancy other than the one treated in this research. Prior history of malignancies, other than low risk MDS or CMML (with less than 5% blasts in bone marrow), unless the patient has been free of the disease for ≥ 3 years. However, patients with the following history/concurrent conditions are allowed:
- •Basal or squamous cell carcinoma of the skin
- •Carcinoma in situ of the cervix
Arms & Interventions
Administration of Oral Azacitidine (CC-486)
Oral azacytidine 300 mg during 14 first days of 28-days cycle for European (EU) patients, Oral azacytidine 200 mg during 14 first days of 28-days cycle for Asian patients (Treatment until progression, patient decision or toxicity)
Intervention: Azacitidine
Investigator's choice therapy - Romidepsin
Romidepsin 14mg/m2 on days 1, 8 and 15 of a 28-days cycle (Treatment until progression, patient decision or toxicity)
Intervention: Romidepsin
Investigator's choice therapy - Gemcitabine
Gemcitabine 1000mg/m2 on days 1, 8 and 15 of a 28-days cycle (during 6 cycles)
Intervention: Gemcitabine
Outcomes
Primary Outcomes
Progression Free Survival (PFS) Based on Local Assessment
Time Frame: From randomization up to documented disease progression or death, whichever occurs first (up to approximately 15 months)
PFS is defined as the time from randomization into the study to the first observation of documented disease progression (local assessment using Lugano Response Criteria 2014) or death due to any cause, whichever occurs first. If a participant has not progressed or died, PFS will be censored at the time of last visit with adequate assessment. C2 censoring rules were used per US FDA guidance 2015. Progression will be determined as per Response criteria for lymphoma: Lugano classification.
Secondary Outcomes
- Time to Response (TTR)(From randomization to the date of attainment of complete response (CR) or partial response (PR) until end of treatment (up to approximately 37 months))
- Overall Survival (OS)(From randomization up to the date of death or date last known alive (up to approximately 27 months))
- Complete Response Rate (CRR)(Response rate will be measured after Cycle 3, after Cycle 6 (up to approximately 5.5 months))
- Progression Free Survival (PFS) Based on IRC Assessment(From randomization up to documented disease progression or death, whichever occurs first (up to approximately 37 months))
- Overall Response Rates (ORR)(Response rate will be measured after Cycle 3, after Cycle 6 (up to approximately 5.5 months))
- Duration of Response (DOR)(From randomization to the date of first documented disease progression, relapse (local assessment) or death from any cause (up to approximately 27 months))
- Progression Free Survival 2 (PFS2) on Local Assessment(From randomization to objective tumor progression on next-line treatment or death from any cause (up to approximately 27 months))
- Mean Change in Minimal Important Differences (MIDs) of the EORTC QLQ-C30 Health-related Quality-of-Life Domain Scores(At baseline and on Day 1 of each cycle up to treatment discontinuation (up to approximately 27 months))